SCELSE Seminar Series: Unravelling the interplay between E. faecalis, neutrophils and shear stress in biofilm-related infections
Date: Thursday, 31 Aug 2023
Time: 10.30am – 11.30am
Venue: NTU School of Biological Sciences Classroom 3 (SBS-01N-23)
Abstract:
Bacteria in our body are adaptable to diverse surfaces, fluid dynamics, nutrient availability, and immune responses. Enterococcus faecalis, a gram-positive pathogen causing infective endocarditis (IE) and catheter-associated urinary tract infections (CAUTI), can forms biofilms on the heart valves and urinary tract, despite fluid flow and immune cell infiltration. Using microfluidic and in vivo models, we aimed to i) identify virulence determinants enabling E. faecalis to establish biofilms under fluid flow and ii) unravel biofilm – innate immunity interplay.
To identify virulence determinants employed under fluid flow, we exposed E. faecalis to fluid flow using microfluidics. RNA-seq unveiled genes linked to adhesion, quorum sensing, and sulfur balance. Notably, OG1RF_11764—a putative adhesion protein—showed significant upregulation, promoting adhesion under shear stress, binding to fibrinogen, and biofilm formation on surfaces. Genes from the fsr operon and gelE were downregulated under fluid flow, enhancing chaining and colonization under flow conditions.
To gain insights into the interplay between biofilms and innate immunity, we employed a microsurgical rat model of IE. Within 6 hours, microcolonies formed on valves, but immune cell infiltration was limited. By 72 hours, large biofilm colonies surrounded by neutrophils releasing NETs appeared, though neutrophil engulfment was rare. In contrast, we found that E. faecalis inhibited NETosis in vitro and is phagocytosed by neutrophils in an opsonization-independent manner. What drives this differential neutrophil response to bacteria in vivo compared to in vitro warrants further investigation.
In summary, our studies provide insights into how bacteria withstand colonization under flow conditions and modulate innate immunity.
Speaker:
DR HARIS ANTYPAS
Senior Research Fellow
Biofilm Biology cluster, SCELSE